The present invention relates to a process and a device for sterilizing and dispensing a liquid for medical use.
Many surgical and medical treatments exist which require the use of large amounts of sterile liquid, in particular of liquid to be injected into a body cavity or into the bloodstream.
For example, mention may be made of haemofiltration, which is one of the treatments used to overcome renal insufficiency. Haemofiltration consists in extracting, from the blood of a patient, by means of ultrafiltration, a determined amount of plasmatic water and in simultaneously infusing the patient with a smaller amount of a so-called substitution solution, which is sterile and contains the main electrolytes of the blood in respective concentrations which are identical or close to those of the blood of a healthy patient. For a four-hour haemofiltration session, it is not uncommon to prescribe an exchange volume for which about sixteen liters to twenty liters of substitution solution are required.
Another example of a treatment which requires the use of a large amount of sterile liquid is automatic peritoneal dialysis. The principle of peritoneal dialysis, the purpose of which is also to overcome renal insufficiency, is to infuse, into the peritoneal cavity of a patient, a determined amount of a sterile solution containing an osmotic agent such as glucose as well as the main electrolytes of the blood in respective concentrations similar to those of the blood of a healthy patient. The solution thus infused is left to stand in contact with the peritoneum, which behaves like a natural dialysis membrane, for the time required for the solution to become optimally enriched in blood impurities (urea, creatinine). The waste solution containing added plasmatic water which the glucose has caused to migrate into the peritoneal cavity is then drained from the patient""s abdomen and is then replaced with fresh solution.
In the standard method of peritoneal dialysis, known as xe2x80x9ccontinuous ambulatory peritoneal dialysis (CAPD)xe2x80x9d, it is the patient himself who carries out the operations of draining and filling his peritoneal cavity, by connecting a drain bag or a solution bag to the end of a catheter permanently installed through his abdominal wall. The transfer of liquid from the peritoneal cavity to the collecting bag and from the bag of solution to the peritoneal cavity takes places by gravity, the collecting bag being kept below the level of the abdomen and the bag filled with fresh solution being kept above the level of the abdomen. Typically, a patient carries out the draining-filling operations which have just been described four to five times a day and each exchange involves two liters of liquid.
In the peritoneal dialysis method known as xe2x80x9cautomatic peritoneal dialysis (APD)xe2x80x9d, the draining-filling operations are carried out overnight, while the patient is resting, using a machine essentially comprising a pump for circulating the drain liquid and the fresh dialysis solution, a heating device for heating the fresh solution, a balance for weighing the bags of fresh solution and of drain liquid and for measuring the weight loss, and a programmable control unit for controlling the alternation of the cycles of dwelling and of draining-filling. Since this mode of treatment is administered by a machine and while the patient is resting, it allows a larger number of exchanges than in standard peritoneal dialysis: five or ten exchanges are usually carried out per night, requiring from ten to thirty liters of fresh solution.
In general, the sterile liquids used for carrying out medical treatments of the type which have just been mentioned are prepared industrially and are packaged in flexible plastic bags. Besides the fact that it is unsuitable for the production of unstable solutions (sodium bicarbonate), this preparations method has several drawbacks, in particular the cost of transporting and storing heavy and bulky bags of solutions and the need to manage products which have expiry dates. To overcome these drawbacks, devices have been proposed for preparing sterile medical liquids at the place of use.
Document EP 0,662,087 describes a process for the on-line preparation of a sterile, pyrogen free liquid which is obtained by filtering a dialysis liquid produced by a standard dialysis machine.
Document GB 2,034,584 describes a process for preparing a sterile liquid whose sterility is obtained by heating the liquid to a determined sterilization temperature for a determined time. A device for carrying out this process, which is designed to fill bags with the sterile liquid, comprises:
heating means for raising the temperature of a liquid immediately upstream of a sterilization unit consisting of a portion of heat-insulated circuit;
a circuit connected to the sterilization unit, which has a first end connected to a source of liquid to be sterilized and a second end connected to a connector which has a first outlet for delivering a sterile liquid;
a discharge pipe connected to a second outlet of the connector, and
pumping means for circulating the liquid in the main circuit.
This device also comprises means for degassing by heating the liquid to be sterilized upstream of the heating means and of the sterilization unit in order to avoid the entrainment of bubbles by the liquid during the sterilization treatment.
Although that document presents the prior degassing as a satisfactory solution to the problem posed by the presence of bubbles in a liquid subjected to a sterilization treatment, it is doubted that, without other precautions, a liquid brought to a high temperature would not entrain bubbles simply because it has been degassed before hand.
Moreover, that document avoids two questions which, according to the invention, need to be answered when the sterilization of a liquid is undertaken. The first question relates to what is meant by the term xe2x80x9csterilizationxe2x80x9d and the second question relates to the microbiological quality of the device used to carry out the sterilization.
It should be recalled that the term xe2x80x9csterilityxe2x80x9d defines a microbiological quality of the object said to be xe2x80x9csterilexe2x80x9d and that, according to standard EN 556 and also according to the US and European Pharmacopoeias, in order for a device or a liquid to be labeled as sterile, it is necessary for the theoretical probability of the presence of a viable microorganism in this device or this liquid to be less than or equal to 10xe2x88x926.
However, checking this 10xe2x88x926 level of presence by examining the finished product is impossible on two counts, both because the sampling required for this check according to the Poisson probability distribution is unachievable, and because, in practical terms, the manipulations required to check the samples entail a probability of contamination which is such that, even if the sampling could be achieved, the results of the check would be erroneous.
One aim of the invention is to produce a sterilization process and a device for carrying out this process which ensure the sterility of the liquid prepared by the device according to the process.
In order to achieve this aim, a device is provided, in accordance with the invention, comprising:
main adjustable heating means for raising the temperature of a liquid inside a heating chamber,
a main circuit comprising:
a first pipe, one end of which can be connected to a source of liquid to be sterilized, and another end of which is connected to an inlet of the heating chamber, and
a second pipe, one end of which is connected to an outlet of the heating chamber, and another end of which is connected to a connector which has a first outlet for delivering a sterile liquid,
first pumping means for circulating the liquid in the main circuit,
characterized in that it comprises:
means for validating a sterilization treatment applied to the liquid, comprising calculation means for calculating a parameter representing the sterilizing value (F0) for the treatment from the value for at least one operating parameter of the device (Q, Tin, THin, Tout, THout), and comparison means for comparing the calculated value of the parameter representing the sterilizing value (F0) to a first threshold value F0min1 corresponding to the sterility of the liquid.
For example, the calculation means are provided to calculate the parameter representing the sterilizing value (F0) for the treatment applied to the liquid from a mathematical model of the temperature distribution in the heating chamber, the temperature (Tin, Tout) of the liquid entering or leaving the heating chamber, the temperature of the heating liquid (THin) and the flow rate of the liquid (Q) in the heating chamber.
According to one characteristic of the invention, the device also comprises control means for controlling the pumping means and/or the heating means such that the calculated value of the parameter representing the sterilizing value (F0) is greater than the first threshold value F0min1.
According to another characteristic of the invention, the device also comprises means for preventing the formation of bubbles in the liquid during the sterilization of the liquid, these means comprising first means, such as a valve with adjustable opening, for adjusting the pressure of the liquid to a pressure value above the vaporization pressure of the liquid, irrespective of the temperature of the liquid, the first means for adjusting the liquid pressure being provided on the second pipe of the main circuit.
According to yet another characteristic of the invention, the device also comprises means for sterilizing the second pipe and the connector comprising:
means for validating a sterilization treatment applied to the second pipe and to the connector, and
means for preventing the formation of bubbles in the liquid during the sterilization of the second pipe and of the connector.
A subject of the invention is also a process consisting in:
heating the liquid in a heating chamber to a temperature and for a period which are suitable for sterilizing the liquid;
validating the sterilization treatment applied to the liquid by calculating a parameter representing the sterilizing value (F0) for the treatment from the value of at least one operating parameter for the device (Q, Tin, THin, Tout, THout), and by comparing the calculated value of the parameter representing the sterilizing value (F0) to a first threshold value F0min1 corresponding to the sterility of the liquid.